Objective To elucidate the function of phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway underlying the regulation of Na+-I-symporter (NIS) and the influence of different levels of iodine on PI3K-AKT signaling pathway in lactating breast cells.Methods The primary cultured mammary gland cells were divided into three groups:①control group [0 μmol/L LY294002 + 0 μg/L insulin-like growth factor Ⅰ (IGF-Ⅰ)];②stimulation group (50 μg/L IGF-Ⅰ);③inhibition group (40 μmo]/L LY294002 + 50 μg/L IGF-Ⅰ).In addition,the cells were treated with different iodine contents (0,5,50,1 000,3 000 μg/L) for low iodine groups 1 and 2,iodine group,high iodine groups 1 and 2,and IGF-Ⅰ (50 μg/L) was used to stimulate PI3K-AKT signaling pathway.The expressions of AKT and NIS mRNA and protein were determined by real-time quantitative PCR and Western blotting,respectively.Results The expression of AKT mRNA (1.497 ± 0.550) in stimulation group was higher than that in inhibition group (0.777 ± 0.108,P ＜ 0.05),while the expression of NIS mRNA and protein in stimulation group (0.783 ± 0.187,0.618 ± 0.103) was lower than those in inhibition group (2.430 ± 1.423,1.417 ± 0.250,all P ＜ 0.05).With the iodine concentration increasing,except high iodine group 1 (1.090 ± 0.356),the expression of AKT mRNA in low iodine groups 1 and 2,iodine group,high iodine group 2 (1.758 ± 0.893,1.320 ± 0.538,1.003 ± 0.006,0.745 ± 0.307) tended to decline;total AKT protein (0.640 ± 0.106,0.601 ± 0.081,0.583 ± 0.089,0.555 ± 0.097,0.532 ± 0.023) and NIS mRNA (2.259 ± 0.682,1.823 ± 0.332,1.409 ± 0.366,1.321 ± 0.405,1.150 ± 0.454) tended to decline in low iodine groups 1 and 2,iodine group,high iodine groups 1 and 2;except low iodine group 2 (0.484 ± 0.179),NIS protein expression tended to decline (0.556 ± 0.199,0.502 ± 0.179,0.455 ± 0.126,0.435 ± 0.138);however,except low iodine group 2 (0.076 ± 0.045),the p-AKT protein expressions (0.078 ± 0.049,0.079 ± 0.040,0.085 ± 0.055,0.095 ± 0.051) were on the rise.Conclusion PI3K-AKT signaling pathway may play an inhibition role in the expression of NIS in lactating breast cells.

Objective:To analyze the application effect of PAD teaching mode in Epidemiology teaching,and to investigate students'suggestions for improving PAD class,so as to provide some thoughts and basis for improving teaching reform.Methods:PAD class was introduced into Epidemiology teaching.Two cross-sectional surveys were conducted after class,and questionnaires about PAD learning interests and suggestions for improvement were anonymously collected.The teaching effect was analyzed and suggestions for rectification were put forward.Results:Among the 134 students majoring in medical laboratory science,the score rate of each learning interest survey item of PAD teaching mode was more than 80% .And 57.46% of the students thought that discussion sessions should be added.The scores of chapter test in PAD mode class was higher than that in traditional mode class(t=2.938,P＜0.01).Conclusions:PAD class can enhance learning interest and knowledge mastery.The time schedule of teaching and discussion should be adjusted in time according to students'wishes,and after-school exercises and counseling should be appropriately increased to promote the application of PAD class in Epidemiology teaching.

Objective:To gain insights into the cognitive processes and utilization patterns of medical students regarding teaching information platforms and resources,and aims to provide valuable references for the implementation of modern medical information technology in educational reforms.Methods:A survey was conducted among all voluntary medical students of grade 2019 to grade 2022.Questionnaire surveys and semi-open interviews were used to investigate.Results:The findings indicated that medical students possess a comprehensive understanding of various teaching platforms,with a high frequency of accessing course materials through these platforms.However,the browsing rate for case analyses recommended by teachers on these platforms remains relatively low.Students demonstrated awareness and utilization of quality courses,particularly MOOCs and micro-courses,which were more frequently utilized compared to other courses.Conclusion:Medical students have a strong awareness of information technology and the ability to solve academic problems through multiple platforms and channels.The construction of teaching platform resources needs to further optimize and improve its simplicity and affinity,and teachers should selectively push high-quality teaching resources to realize the rational application of medical information technology in teaching.

Objective: To explore the effects of vitamin D₃ on intestinal mucosal barrier of mice with severe burns. Methods: Forty-two C57BL/6C male mice aged eight to twelve weeks were divided into vitamin D₃ vehicle+ sham injury group of seven mice, vitamin D₃ vehicle+ burn injury group of fourteen mice, vitamin D₃+ sham injury group of seven mice, and vitamin D₃+ burn injury group of fourteen mice according to random number table. Mice in vitamin D₃ vehicle+ sham injury group and vitamin D₃ vehicle+ burn injury group were injected with vehicle of vitamin D₃ at a dose of 0.1 mL intraperitoneally at 1, 24, and 48 h before burn experiment. Mice in vitamin D₃+ sham injury group and vitamin D₃+ burn injury group were injected with vitamin D₃ at a dose of 100 ng/kg dissolved in 0.1 mL vehicle intraperitoneally at the same time points. Mice in vitamin D₃ vehicle+ burn injury group and vitamin D₃+ burn injury group were inflicted with 30% total body surface area full-thickness dermal scald (hereinafter referred to as burn) on the back by 98 ℃ hot water for 3 to 4 seconds. And mice in vitamin D₃ vehicle+ sham injury group and vitamin D₃+ sham injury were treated with 37 ℃ water on the back for 3 to 4 seconds to simulate injury. Seven mice in vitamin D₃ vehicle+ sham injury group and seven mice in vitamin D₃+ sham injury group at post injury hour (PIH) 24, and seven mice in vitamin D₃ vehicle+ burn injury group and seven mice in vitamin D₃+ burn injury group at PIH 6 and 24 were sacrificed respectively to collect mesentery lymph nodes, spleens, livers, and intestinal tissue. The mesentery lymph nodes, spleens, and livers of mice in each group were collected to observe growth of bacteria, and number of bacteria was counted. Intestinal tissue of mice in each group was collected to detect protein expressions of zonal occludin 1 (ZO-1) and occludin by immunohistochemistry staining method, distribution of ZO-1 by immunofluorescence staining method, and expression of occludin by Western blotting. Data were processed with Kruskal-Wallis H test, Nemenyi test, one-way analysis of variance, t test, and Bonferroni correction. Results: (1) At PIH 6 and 24, bacterial counts of mesentery lymph nodes, livers, and spleens of mice in vitamin D₃ vehicle+ burn injury group were significantly higher than those of mice in vitamin D₃ vehicle+ sham injury group (P<0.05). At PIH 6, bacterial counts of livers and spleens of mice in vitamin D₃+ burn injury group were significantly lower than those of mice in vitamin D₃ vehicle+ burn injury group (P<0.05). At PIH 24, bacterial counts of mesentery lymph nodes and livers of mice in vitamin D₃+ burn injury group were significantly lower than those of mice in vitamin D₃ vehicle+ burn injury group (P<0.05). (2) At PIH 6 and 24, expressions of ZO-1 and occludin of intestinal tissue of mice in vitamin D₃ vehicle+ burn injury group were significantly lower than those of mice in vitamin D₃ vehicle+ sham injury group, and expressions of ZO-1 and occludin of intestinal tissue of mice in vitamin D₃+ burn injury group were close to those of mice in vitamin D₃+ sham injury group. At PIH 6 and 24, expressions of ZO-1 and occludin of intestinal tissue of mice in vitamin D₃+ burn injury group were significantly higher than those of mice in vitamin D₃ vehicle+ burn injury group. (3) At PIH 6 and 24, compared with that of mice in vitamin D₃ vehicle+ sham injury group, distribution of ZO-1 of intestinal mucosal epithelium of mice in vitamin D₃ vehicle+ burn injury group was discontinuous. Distribution of ZO-1 of intestinal mucosal epithelium of mice in vitamin D₃+ sham injury group was normal, and the distribution of ZO-1 of intestinal mucosal epithelium of mice in vitamin D₃+ burn injury group was with good continuity. (4) At PIH 6 and 24, expressions of occludin of intestinal tissue of mice in vitamin D₃ vehicle+ burn injury group were 0.720±0.003, 0.638±0.052 respectively, significantly lower than 0.918±0.003 of mice in vitamin D₃ vehicle+ sham injury group (t=57.33, 5.36, P<0.05). At PIH 6 and 24, expressions of occludin of intestinal tissue of mice in vitamin D₃+ burn injury group were 0.994±0.058, 1.064±0.060, close to 0.938±0.023 of mice in vitamin D₃+ sham injury group (t=0.91, 1.96, P>0.05). At PIH 6 and 24, expressions of occludin of intestinal tissue of mice in vitamin D₃ vehicle+ burn injury group were significantly lower than those of mice in vitamin D₃+ burn injury group (t=4.75, 5.35, P<0.05). Conclusions Intestinal bacterial translocation can occur in the early stage of severe burn. And vitamin D₃ plays a protective role in the intestinal mucosal barrier post severe burn to reduce the bacterial translocation by protecting tight junction proteins of intestinal epithelium.

OBJECTIVESince 1986, the reference of birth weight for gestational age has not been updated. The aim of this study was to set up Chinese neonatal network to investigate the current situation of birth weight in China, especially preterm birth weight, to develop the new reference for birth weight for gestational age and birth weight curve.

METHODA nationwide neonatology network was established in China. This survey was carried out in 63 hospitals of 23 provinces, municipalities and autonomous regions. We continuously collected the information of live births in participating hospitals during the study period of 2011-2014. Data describing birth weight and gestational age were collected prospectively. Newborn's birth weight was measured by electronic scale within 2 hours after birth when baby was undressed. The evaluation of gestational age was based on the combination of mother's last menstrual period, ultrasound in first trimester and gestational age estimation by gestational age scoring system.

STATISTICAL ANALYSISthe growth curve was drawn by using LMSP method, which was conducted in GAMLSS 1.9-4 software package in R software 2.11.1.

RESULTA total of 159 334 newborn infants were enrolled in this study. There were 84 447 male and 74 907 female. The mean birth weight was (3 232 ± 555) g, the mean birth weight of male newborn was (3 271 ± 576) g, the mean weight of female newborn was (3 188 ± 528) g. The test of the variables' distribution suggested that the distribution of gestational age and birth weight did not fit the normal distribution, the optimal distribution for them was BCT distribution. The Q-Q plot test and worm plot test suggested that this curve fitted the distribution optimally. The male and female neonatal birth weight curve was developed using the same method.

CONCLUSIONUsing GAMLSS method to establish nationwide neonatal birth weight curve, and the first time to update the birth weight reference in recent 28 years.

Birth Weight ; China ; Female ; Gestational Age ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Male

Objective:To observe the mRNA and protein expression levels of thyroid stimulating hormone receptor (TSHR), protein kinase A (PKA) and sodium iodine transporter (NIS) in mammary gland tissue of lactating rats with different iodine nutrition levels, and to explore the role of thyroid stimulating hormone (TSH)-THSR-cyclic adenosine monophosphate (cAMP)-PKA signal pathway in the process of mammary iodine uptake during lactation.Methods:Using a group design, according to body weight (80 - 100 g), 110 Wistar female rats were randomly divided into normal iodine (NI) group, severe iodine deficiency (SID) group, moderately iodine deficiency (MID) group, moderately iodine excess (MIE) group and severe iodine excess (SIE) group, with 22 rats in each group. Another 22 Wistar male rats were selected, and the feeding situation was consistent with that of NI group. After 3 months of feeding, 24-hour urine samples of female rats were collected, and the female rats were caged with the male rats (5 ∶ 1). After mating, each female rat was fed separately. At 10 days of childbirth, the lactating rats were sacrificed and thyroid and mammary gland tissues were taken. The urinary iodine was determined by arsenic cerium catalytic spectrophotometry. The morphological changes of thyroid and mammary gland tissues were observed by HE staining. The mRNA expression levels of TSHR, PKA and NIS in thyroid and mammary gland tissues were measured by real-time PCR; the protein expression levels of TSHR, PKA, phosphorylated PKA (p-PKA), and NIS in mammary gland tissue were measured by Western blotting.Results:Compared with NI group (162.59 μg/L), the median urinary iodine of female rats in SID and MID groups (3.16, 6.36 μg/L) was lower, and the median urinary iodine of female rats in MIE and SIE groups (2 356.27, 11 507.29 μg/L) was higher ( P < 0.01). HE staining showed that different levels of iodine uptake had different effects on thyroid follicles: most of the follicles in NI group were uniform round or oval; in MID group, the number of small follicles increased, the epithelial cells were monolayer columnar or cubic, the follicular cavity became smaller, and the glia decreased; the follicles in SID group became smaller, and the epithelial cells were columnar or high columnar, with reduced or absent glia in the follicular cavity; pleomorphic changes were found in thyroid follicles in SIE and MIE groups, with some follicles significantly enlarged and some small follicles hyperplasia. Different levels of iodine intake had different effects on mammary duct: compared with NI group, the connective tissue around the mammary duct in SID and MID groups showed obvious fibrosis, while the fibrosis in MIE and SIE groups was significantly reduced. The results of real-time PCR showed that there were significant differences in the mRNA expression levels of TSHR, PKA and NIS in thyroid tissues of lactating rats with different levels of iodine nutrition ( F = 10.73, 92.37, 115.75, P < 0.01). There were statistically differences in the mRNA expression levels of TSHR, PKA and NIS in mammary gland tissues of lactating rats with different levels of iodine nutrition ( F = 40.25, 39.63, 14.92, P < 0.05). Western blotting results showed that there were significant differences in the protein expression levels of TSHR, PKA, p-PKA and NIS in mammary gland tissues of lactating rats with different levels of iodine nutrition ( F = 4.14, 6.73, 8.48, 4.51, P < 0.05). Among them, the protein expression level of TSHR in MIE and SIE groups was lower than that in NI group ( P < 0.05); the protein expression level of PKA in SID and MID groups was higher than that in NI group ( P < 0.05); the protein expression level of p-PKA in SID group was higher than that in NI group, but that in SIE group was lower than that in NI group ( P < 0.05), the protein expression level of NIS in SID group was higher than that in NI group ( P < 0.05). Conclusions:The mRNA and protein expression levels of TSHR are decreased in mammary gland tissues of lactating rats with high iodine intake, while the mRNA and protein expression levels of PKA and NIS are increased in low iodine intake. TSH-TSHR-cAMP-PKA signal pathway may be involved in the regulation of iodine intake in mammary gland tissue of lactating rats, which may protect itself and its offspring.

Objective A competing endogenous RNA (ceRNA) regulatory network associated with long non-coding RNA (lncRNA) specific for lung adenocarcinoma (LUAD) was constructed based on bioinformatics methods, and the functional mechanism of actinfilament-associated protein 1-antisense RNA1 (AFAP1-AS1) in LUAD was analyzed, in order to provide a new direction for the study of LUAD therapeutic targets. Methods The gene chip of LUAD was downloaded from the Gene Expression Omnibus (GEO), and lncRNA and mRNA with differential expression between LUAD and normal tissues were screened using GEO2R online software, and their target genes were predicted by online databases to construct ceRNA networks and perform enrichment analysis. In cell experiments, AFAP1-AS1 was genetically knocked down and siRNA was constructed and transfected into LUAD cells A549 by cell transfection. CCK8, transwell, scratch assay and flow cytometry were used to detect the ability of cells to proliferate, invade, migrate and apoptosis. Results A total of 6 differentially expressed lncRNA and 494 differentially expressed mRNA were identified in the microarray of LUAD. The ceRNA network involved a total of 6 lncRNA, 22 miRNA, and 55 mRNA. Enrichment analysis revealed that mRNA was associated with cancer-related pathways. In cell assays, knockdown of AFAP1-AS1 inhibited cell proliferation, invasion, and migration, and AFAP1-AS1 promoted apoptosis. Conclusion In this study, we construct a lncRNA-mediated ceRNA network, which may help to further investigate the mechanism of action of LUAD. In addition, through cellular experiments, AFAP1-AS1 is found to have potential as a therapeutic target for LUAD.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.